Search

Background Maternity providers, including nurses, midwives, physicians, are at significant risk for stress and burnout due to the nature of care provision in maternal and child health settings. Yet, the empirical evidence on stress and burnout among maternity providers in sub-Saharan Africa is scarce. Therefore, the purpose of our study was to (1) assess levels of stress and burnout among maternity providers and support staff in Ghana, and (2) identify individual and situational factors associated with maternity provider stress, burnout, and physiology. Method Using a purposive sampling technique, we recruited 150 maternity providers from 19 high delivery health facilities within the 15 districts of the Upper East region (UER) of Ghana into a cross-sectional study. Participants completed Cohen’s Perceived Stress Scale, the Shirom-Melamed Burnout scale, and sociodemographic, health-, and work-related items. Participants’ heart rate variability (HRV) and hair cortisol levels were assessed for stress-related physiologic responses. We computed bivariate and multivariate linear regression models to examine factors associated with stress and burnout. Result Most participants were experiencing moderate to high stress (58.0%) and burnout (65.8%). Each unit increase in overcommitment to work was associated with 0.62 higher perceived stress scores (β = 0.62, 95% CI: 0.22, 1.02) and 0.15 higher burnout scores. On average, those who had experienced disrespect from colleagues in the last year had higher perceived stress scores compared to those who had not experienced disrespect (β = 1.77, 95% CI: 0.50, 3.04); and those who had experienced disrespect from patients in the last year had higher cortisol levels than those who had not (β = 0.52, 95% CI: 0.11, 0.93). Those who work for more than 5 days also had higher cortisol levels, on average, compared to those who worked fewer days a week. Conclusion We found high levels of stress and burnout among maternity providers in Northern Ghana, underscoring the need for interventions to manage the effects of stress and burnout on maternity providers’ wellbeing, quality of care, and patient outcomes. Healthcare management teams should assist providers in reducing their overcommitment by hiring more staff, given its strong link to stress and burnout. Additionally, facilitating a respectful workplace culture could also help reduce stress and burnout among maternity providers.

Background Perinatal mortality remains high globally and remains an important indicator of the quality of a health care system. To reduce this mortality, it is important to provide the recommended care during the perinatal period. We assessed the prevalence and factors associated with appropriate perinatal care (antenatal, intrapartum, and postpartum) in Bunyoro region, Uganda. Results from this study provide valuable information on the perinatal care services and highlight areas of improvement for better perinatal outcomes. Methods A cross sectional survey was conducted among postpartum mothers attending care at three district hospitals in Bunyoro. Following consent, a questionnaire was administered to capture the participants’ demographics and data on care received was extracted from their antenatal, labour, delivery, and postpartum records using a pre-tested structured tool. The care received by women was assessed against the standard protocol established by World Health Organization (WHO). Poisson regression with robust standard errors was used to assess factors associated with appropriate postpartum care. Results A total of 872 mothers receiving care at the participating hospitals between March and June 2020 were enrolled in the study. The mean age of the mothers was 25 years (SD = 5.95). None of the mothers received appropriate antenatal or intrapartum care, and only 3.8% of the participants received appropriate postpartum care. Factors significantly associated with appropriate postpartum care included mothers being >35 years of age (adjusted prevalence ratio [aPR] = 11.9, 95% confidence interval [CI] 2.8–51.4) and parity, with low parity (2–3) and multiparous (>3) mothers less likely to receive appropriate care than prime gravidas (aPR = 0.3, 95% CI 0.1–0.9 and aPR = 0.3, 95% CI 0.1–0.8 respectively). Conclusions Antenatal, intrapartum, and postpartum care received by mothers in this region remains below the standard recommended by WHO, and innovative strategies across the continuum of perinatal care need to be devised to prevent mortality among the mothers. The quality of care also needs to be balanced for all mothers irrespective of the age and parity.

Objective A screening centre in Soweto, South Africa (SA), investigated high-risk human papillomavirus (HR-HPV), HIV, cervical cancer risk amongst women. Methods This cross-sectional study (June 2018-March 2019) describes screening results (Roche Linear Array HPV test and Pap smear liquid based cytology) and history of screening (known HIV status, antiretroviral therapy [ART] use, previous Pap smears). Data were stratified by age group (18–29, 30+ years), HIV status, Pap smear results and tested for statistical significance. Results Of 280 women, 20.4% were HIV-positive, 18.2% had abnormal Pap smears, 41.8% had HR-HPV. Of older women, 48.2% (n = 78/162) had never had a Pap smear. Of younger women, 89.0% (n = 105/118) never had a Pap smear, but had significantly more low-grade squamous intraepithelial lesions (LSIL) and other HR-HPV infection than older women (12.7%[n = 15/118] vs 4.9%[n = 8/162], p = 0.0193; and 49.2%[n = 58/118] vs 29.0%[n = 47/162], p = 0.0006; respectively). HIV-positive women had more abnormal cytology results and infection with other HR-HPV types or co-infection with other HR-HPV type(s)/HPV-16 compared to HIV-negative women (35.1%[n = 20/57] vs 13.9%[n = 31/223], p = 0.0002; 56.1%[n = 32/57] vs 32.7%[n = 73/223], p = 0.001; and 12.3%[n = 7/57] vs 4.9%[n = 11/223], p = 0.044; respectively). Of 57 HIV-positive women, 45.6% (n = 26) already knew their HIV status; of which 69.2% were on ART and 34.6% never had a Pap smear. Conclusion South African women have high rates of HIV, Pap smear abnormalities and HR-HPV, with low cervical cancer screening coverage. SA cervical cancer screening policy excludes (undiagnosed) HIV-positive and HIV-negative women

Background Intermittent claudication (IC) is a common manifestation of peripheral arterial disease. Some patients with IC experience a rise in Urinary N-acetyl-β-D-Glucosaminidase (NAG)/ Creatinine (Cr) ratio, a marker of renal injury, following exercise. In this study, we aim to investigate whether peripheral blood mononuclear cells (PBMC) from patients with IC who exhibit a rise in urinary NAG/ Cr ratio following exercise exhibit differential IL-10/ IL-12 ratio and gene expression compared to those who do not have a rise in NAG/ Cr ratio. Methods We conducted a single center observational cohort study of patients diagnosed with IC. Blood and urine samples were collected at rest and following a standardised treadmill exercise protocol. For comparative analysis patients were separated into those with any rise in NAG/Cr ratio (Group 1) and those with no rise in NAG/Cr ratio (Group 2) post exercise. Isolated PBMC from pre- and post-exercise blood samples were analysed using flow cytometry. PBMC were also cultured for 20 hours to perform further analysis of IL-10 and IL-12 cytokine levels. RNA-sequencing analysis was performed to identify differentially expressed genes between the groups. Results 20 patients were recruited (Group 1, n = 8; Group 2, n = 12). We observed a significantly higher IL-10/IL-12 ratio in cell supernatant from participants in Group 1, as compared to Group 2, on exercise at 20 hours incubation; 47.24 (IQR 9.70–65.83) vs 6.13 (4.88–12.24), p = 0.04. 328 genes were significantly differentially expressed between Group 1 and 2. The modulated genes had signatures encompassing hypoxia, metabolic adaptation to starvation, inflammatory activation, renal protection, and oxidative stress. Discussion Our results suggest that some patients with IC have an altered immune status making them ‘vulnerable’ to systemic inflammation and renal injury following exercise. We have identified a panel of genes which are differentially expressed in this group of patients.

Background Few studies have analysed the effect of HIV universal test and treat (UTT) on retention and mortality among people living with HIV (PLHIV) in routine care. We examined six-month retention and mortality at 11 health facilities (HFs) run by a large NGO, The AIDS Support Organisation (TASO), before and after UTT. Methods We used a quasi-experimental study using patient data extracted from 11 TASO HFs. Two periods, one before UTT (2015–2016) and the other during UTT (2017–2018) were compared. The primary outcome was six-month retention defined as the proportion of PLHIV who were alive and in care at six months from enrolment. The secondary outcome was six-month mortality defined as the proportion of PLHIV who died within six months from enrolment. We performed an interrupted time series analysis using graphical aids to study trends in six-month retention and mortality and a segmented regression to evaluate the effect of UTT. We used a generalized linear mixed model (GLMM) and generalized estimating equations (GEE) to account for facility-level clustering. Results Of the 20,171 PLHIV registered between 2015 and 2018 and included in the analysis, 12,757 (63.2%) were enrolled during the UTT period. 5256/7414 (70.9%) of the pre-UTT period compared to 12239/12757 (95.9%) of the UTT were initiated on ART treatment with 6 months from enrolment. The median time from enrolment to initiating ART was 14 (interquartile range (IQR): 0–31) days for the pre-UTT compared to 0 (IQR: 0–0) days for the UTT period. The median age at enrolment was 32.5 years for the pre-UTT and 35.0 years for the UTT period. Overall, the six-month retention just after scale-up of UTT, increased by 9.2 percentage points (p = 0.002) from the baseline value of 82.6% (95% CI: 77.6%-87.5%) but it eventually decreased at a rate 1.0 percentage point (p = 0.014) for cohorts recruited each month after UTT. The baseline six-month mortality was 3.3% (95% CI: 2.4%-4.2%) and this decreased by 1.6 percentage points (p = 0.003) immediately after UTT. The six-month mortality continued decreasing at a rate of 0.1 percentage points (p = 0.002) for cohorts enrolled each month after UTT. Retention differed between some health facilities with Rukungiri HF having the highest and Soroti the lowest retention. Retention was slightly higher among males and younger people. Mortality was highest among people aged 50 years and more. The effect of UTT on retention and mortality was similar across sex and age groups. Conclusion Overall, UTT significantly led to an immediate increase in retention and decrease in mortality among PLHIV enrolled in HIV care from 11 HFs run by TASO in Uganda. However, retention (and mortality) significantly decreased for cohorts enrolled each month after UTT. Retention was highest in Rukungiri and lowest in Soroti HFs and slightly higher in males and younger people. Mortality was highest in older patients and lowest in adolescents. We recommend for innovative interventions to improve the overall retention particularly in facilities reporting low retention in order to achieve the UNAIDS 2030 target of 95-95-95.

Funder: school of tropical medicine and global health, nagasaki university, BACKGROUND: Since the COVID-19 pandemic began, there have been concerns related to the preparedness of healthcare workers (HCWs). This study aimed to describe the level of awareness and preparedness of hospital HCWs at the time of the first wave. METHODS: This multinational, multicenter, cross-sectional survey was conducted among hospital HCWs from February to May 2020. We used a hierarchical logistic regression multivariate analysis to adjust the influence of variables based on awareness and preparedness. We then used association rule mining to identify relationships between HCW confidence in handling suspected COVID-19 patients and prior COVID-19 case-management training. RESULTS: We surveyed 24,653 HCWs from 371 hospitals across 57 countries and received 17,302 responses from 70.2% HCWs overall. The median COVID-19 preparedness score was 11.0 (interquartile range [IQR] = 6.0-14.0) and the median awareness score was 29.6 (IQR = 26.6-32.6). HCWs at COVID-19 designated facilities with previous outbreak experience, or HCWs who were trained for dealing with the SARS-CoV-2 outbreak, had significantly higher levels of preparedness and awareness (p

Background Nodding syndrome (NS), is an unexplained form of epilepsy which leads to stunted growth, cognitive decline, and a characteristic nodding of the head. Current data about its impact on households in Uganda is scarce. Therefore, this study aims to assess the economic burden of the persistent morbidity of NS on caregivers in affected households in Northern Uganda. Methods A cross-sectional cost-of-care study was conducted from January 2019 to February 2019 in Lakwela village-Northern Uganda in 14 households, who are members of a community-based organization(CBO)established in the village with the support of a Japanese research team, (Uganda-Japan Nodding Syndrome Network).Data was collected through questionnaires. Both direct (medical and non-medical) and indirect (informal care) costs of caregiving were assessed. Indirect costs were valued using the human-capital method as loss of production. Results Direct costs constituted a higher proportion of costs for NS households, accounting for on average 7.7% of household expenditure. The annual weighted mean cost per NS patient was estimated at 27.6 USD (26.4 USD direct costs, 96.2% and 1.2 USD indirect cost, 3.8%). Average time spent on informal caregiving was 4.4 ±1.7 (standard deviation) hours/ week with an estimated annual informal caregiving cost of 24.85 USD and gross domestic product (GDP) loss of 412.40 USD. Conclusion Direct costs due to NS are still high among households in this study. More studies are needed to investigate measures that could help bring down these costs and equally reduce the day-to-day disruption of caregiver’s activities; consequently, improving the lives of these affected households and communities., PLoS ONE, 15, art.no.e0238643; 2020

A fluorescence marker mOrange was inserted to the popular pLentiCrispr-V2 to create pLentiCrispr-V2-mOrange (V2mO) that contained both a puromycin selection and a fluorescent marker, making viral production and target transduction visible. Lentiviruses packaged with this plasmid and appropriate guide RNAs (gRNAs) successfully knocked out the genes RhoA, Gli1, and Gal3 in human gastric cancer cell lines. Cas9-gRNA editing efficiency could be estimated directly from Sanger electropherograms of short polymerase chain reaction products around the gRNA regions in Cas9-gRNA transduced cells. Single cloning of transduced target cell pools must be performed to establish stable knockout clones. Rescue of wildtype (RhoA and Gal3) and mutant (RhoA.Y42C) genes into knockout cells was successful only when cDNAs, where gRNAs bind, were modified by three nucleotides while the amino acid sequences remained unchanged. Stringent on-target CRISPR/Cas9 editing was observed in Gal3 gene, but not in RhoA gene since RhoA.Y42C already presented a nucleotide change in gRNA5 binding site. In summary, our improved strategy added these advantages: adding visual marker to the popular lentiviral system, monitoring lentiviral production and transduction efficiencies, cell-sorting Cas9+ cells in target cells by fluorescence-activated cell sorting, direct estimation of gene editing efficiency of target cell pools by short PCR electropherograms around gRNA binding sites, and successful rescue of wildtype and mutant genes in knockout cells, overcoming Cas9 editing by modifying cDNAs.

IntroductionSouth Africa is the HIV epidemic epicentre; however, non-communicable diseases (NCDs) will be the most common cause of death by 2030. To improve identification and initiation of care for HIV and NCDs, we assessed proportion of clients referred and linked to care (LTC) for abnormal/positive screening results and time to LTC and treatment initiation from a HIV Testing Services (HTS) Centre before and after integrated testing for NCDs with optional peer-navigated linkage to care.Materials and methodsThis two-phase prospective study was conducted at an adult HTS Centre in Soweto, South Africa. Phase 1 (February-June 2018) utilised standard of care (SOC) HTS services (blood pressure [BP], HIV rapid diagnostic testing (RDT), sexually transmitted infections [STI]/Tuberculosis [TB] symptom screening) with passive referral for abnormal/positive results. Phase 2 (June 2018-March 2019) further integrated blood glucose/cholesterol/chlamydia RDT, with optional peer-navigated referral. Enrolled referred clients completed telephonic follow-up surveys confirming LTC/treatment initiation ≤3 months post-screening. Socio-demographics, screening results, time to LTC/treatment initiation, peer-navigated referral uptake were reported. Analysis included Fisher's exact, chi-squared, Kruskal Wallis, and Student's T-tests. Thematic analysis was conducted for open-ended survey responses.ResultsOf all 320 referrals, 40.0% were HIV-infections, 11.9% STIs, 6.6% TB, and 28.8% high/low BP. Of Phase 2-only referrals, 29.4% were for glucose and 23.5% cholesterol. Integrated NCD-HTS had significantly more clients LTC for HIV (76.7%[n = 66/86] vs 52.4%[n = 22/42], p = 0.0052) and within a shorter average time (6-8 days [Interquartile range (IQR):1-18.5] vs 8-13 days [IQR:2-32]) as compared to SOC HTS. Integrated NCD-HTS clients initiated HIV/STIs/BP treatment on average more quickly as compared to SOC HTS (5 days for STIs [IQR:1-21], 8 days for HIV/BP [IQR:5-17 and 2-13, respectively] vs 10 days for STIs [IQR: 4-32], 19.5 days for HIV [IQR:6.5-26.5], 8 days for BP [IQR:2-29)]. Participants chose passive over active referral (89.1% vs 10.9%; pConclusionSame-day treatment initiation is not achieved across diseases, despite peer-navigated referral. There are psychosocial and health systems barriers at entry to care/treatment initiation. Additional research may identify best strategies for rapid treatment initiation.

Poliovirus (PV) environmental surveillance (ES) plays an important role in the global eradication program and is crucial for monitoring silent PV circulation especially as clinical cases decrease. This study compared ES results using the novel bag-mediated filtration system (BMFS) with the current two-phase separation method. From February to November 2016, BMFS and two-phase samples were collected concurrently from twelve sites in Pakistan (n = 117). Detection was higher in BMFS than two-phase samples for each Sabin-like (SL) PV serotype (p

Background HIV drug resistance (HIVDR) poses a threat to future antiretroviral therapy success. Monitoring HIVDR patterns is of particular importance in populations such as sex workers (SWs), where documented HIV prevalence is between 34–89%, and in countries with limited therapeutic options. Currently in South Africa, there is a dearth in evidence and no ongoing surveillance of HIVDR amongst sex work populations. This study aims to describe the prevalence of HIVDR amongst a sample of female sex workers (FSWs) from Soweto, South Africa. Methodology A cross-sectional, respondent driven sampling (RDS) recruitment methodology was used to enrol FSWs based in Soweto. Participants were tested for HIV and undertook a survey that included HIV knowledge and treatment status. Whole blood specimens were collected from HIV positive FSWs to measure for CD4 counts, viral load (VL) and perform HIVDR genotyping. Frequencies were determined for categorical variables and medians and interquartile ranges (IQR) for the continuous. Results Of the 508 enrolled participants, 55% (n = 280) were HIV positive and of median age 32 (IQR: 20–51) years. Among the HIV positive, 51.8% (132/269) were defined as virologically suppressed (VL < 400 copies/ml). Of the 119 individuals with unsuppressed viral loads who were successfully genotyped for resistance testing 37.8% (45/119) had detectable drug resistance. In this group, HIVDR mutations were found amongst 73.7% (14/19) of individuals on treatment, 27.4% (26/95) of individuals who were treatment naive, and 100% (5/5) of defaulters. One phylogenetic cluster was found amongst treatment naive FSWs. The K103N mutation was detected most commonly in 68.9% (31/45) individuals with HIVDR mutations, with 20/26 (76.9%) of treatment naive FSW with detectable resistance having this mutation. The M184V mutation was found in both FSWs on treatment (12/14, 85.7%) and those defaulting (1/5, 20.0%). Discussion More than one third (45/119) of the genotyped sample had HIVDR, with resistance to the NNRTI class being the most common. Almost half of HIV positive FSWs had unsuppressed viral loads, increasing the likelihood for onward transmission of HIV. Disturbingly, more than 1:4 treatment naive women with unsuppressed viral loads had HIVDR suggesting that possible sexual transmission of drug resistance is occurring in this high-risk population. Given the high burden of HIVDR in a population with a high background prevalence of HIV, it is imperative that routine monitoring of HIVDR be implemented. Understanding transmission dynamics of HIVDR in FSW and its impact on treatment success should be urgently elucidated.

MRI has recently been applied as a tool to quantitatively evaluate the response to therapy in patients with Crohn's disease, and is the preferred choice for repeated imaging. Bowel wall thickness on MRI is an important biomarker of underlying inflammatory activity, being abnormally increased in the acute phase and reducing in response to successful therapy; however, a poor level of interobserver agreement of measured thickness is reported and therefore a system for accurate, robust and reproducible measurements is desirable. We propose a novel method for estimating bowel wall-thickness to improve the poor interobserver agreement of the manual procedure. We show that the variability of wall thickness measurement between the algorithm and observer measurements (0.25mm ± 0.81mm) has differences which are similar to observer variability (0.16mm ± 0.64mm).

Background\ud \ud Alternating hemiplegia of childhood is a very rare and serious neurodevelopmental syndrome; its genetic basis has recently been established. Its characteristic features include typically-unprovoked episodes of hemiplegia and other transient or more persistent neurological abnormalities.\ud \ud Methods\ud \ud We used transcranial magnetic stimulation to assess the effect of the condition on motor cortex neurophysiology both during and between attacks of hemiplegia. Nine people with alternating hemiplegia of childhood were recruited; eight were successfully tested using transcranial magnetic stimulation to study motor cortex excitability, using single and paired pulse paradigms. For comparison, data from ten people with epilepsy but not alternating hemiplegia, and ten healthy controls, were used.\ud \ud Results\ud \ud One person with alternating hemiplegia tested during the onset of a hemiplegic attack showed progressively diminishing motor cortex excitability until no response could be evoked; a second person tested during a prolonged bilateral hemiplegic attack showed unusually low excitability. Three people tested between attacks showed asymptomatic variation in cortical excitability, not seen in controls. Paired pulse paradigms, which probe intracortical inhibitory and excitatory circuits, gave results similar to controls.\ud \ud Conclusions\ud \ud We report symptomatic and asymptomatic fluctuations in motor cortex excitability in people with alternating hemiplegia of childhood, not seen in controls. We propose that such fluctuations underlie hemiplegic attacks, and speculate that the asymptomatic fluctuation we detected may be useful as a biomarker for disease activity.\ud

Neurons innervating the airways contribute to airway hyperreactivity (AHR), a hallmark feature of asthma. Several observations suggested that acid-sensing ion channels (ASICs), neuronal cation channels activated by protons, might contribute to AHR. For example, ASICs are found in vagal sensory neurons that innervate airways, and asthmatic airways can become acidic. Moreover, airway acidification activates ASIC currents and depolarizes neurons innervating airways. We found ASIC1a protein in vagal ganglia neurons, but not airway epithelium or smooth muscle. We induced AHR by sensitizing mice to ovalbumin and found that ASIC1a-/- mice failed to exhibit AHR despite a robust inflammatory response. Loss of ASIC1a also decreased bronchoalveolar lavage fluid levels of substance P, a sensory neuropeptide secreted from vagal sensory neurons that contributes to AHR. These findings suggest that ASIC1a is an important mediator of AHR and raise the possibility that inhibiting ASIC channels might be beneficial in asthma.

Despite significant advances in tissue engineering such as the use of scaffolds, bioreactors and pluripotent stem cells, effective cardiac tissue engineering for therapeutic purposes has remained a largely intractable challenge. For this area to capitalise on such advances, a novel approach may be to unravel the physiological mechanisms underlying the development of tissues that exhibit rhythmic contraction yet do not originate from the cardiac lineage. Considerable attention has been focused on the physiology of the avian lymph heart, a discrete organ with skeletal muscle origins yet which displays pacemaker properties normally only found in the heart. A functional lymph heart is essential for avian survival and growth in ovo. The histological nature of the lymph heart is similar to skeletal muscle although molecular and bioelectrical characterisation during development to assess mechanisms that contribute towards lymph heart contractile rhythmicity have not been undertaken. A better understanding of these processes may provide exploitable insights for therapeutic rhythmically contractile tissue engineering approaches in this area of significant unmet clinical need. Here, using molecular and electrophysiological approaches, we describe the molecular development of the lymph heart to understand how this skeletal muscle becomes fully functional during discrete in ovo stages of development. Our results show that the lymph heart does not follow the normal transitional programme of myogenesis as documented in most skeletal muscle, but instead develops through a concurrent programme of precursor expansion, commitment to myogenesis and functional differentiation which offers a mechanistic explanation for its rapid development. Extracellular electrophysiological field potential recordings revealed that the peak-to-peak amplitude of electrically evoked local field potentials elicited from isolated lymph heart were significantly reduced by treatment with carbachol; an effect that could be fully reversed by atropine. Moreover, nifedipine and cyclopiazonic acid both significantly reduced peak-to-peak local field potential amplitude. Optical recordings of lymph heart showed that the organ's rhythmicity can be blocked by the HCN channel blocker, ZD7288; an effect also associated with a significant reduction in peak-to-peak local field potential amplitude. Additionally, we also show that isoforms of HCN channels are expressed in avian lymph heart. These results demonstrate that cholinergic signalling and L-type Ca2+ channels are important in excitation and contraction coupling, while HCN channels contribute to maintenance of lymph heart rhythmicity.

Background Alternating hemiplegia of childhood is a very rare and serious neurodevelopmental syndrome; its genetic basis has recently been established. Its characteristic features include typically-unprovoked episodes of hemiplegia and other transient or more persistent neurological abnormalities. Methods We used transcranial magnetic stimulation to assess the effect of the condition on motor cortex neurophysiology both during and between attacks of hemiplegia. Nine people with alternating hemiplegia of childhood were recruited; eight were successfully tested using transcranial magnetic stimulation to study motor cortex excitability, using single and paired pulse paradigms. For comparison, data from ten people with epilepsy but not alternating hemiplegia, and ten healthy controls, were used. Results One person with alternating hemiplegia tested during the onset of a hemiplegic attack showed progressively diminishing motor cortex excitability until no response could be evoked; a second person tested during a prolonged bilateral hemiplegic attack showed unusually low excitability. Three people tested between attacks showed asymptomatic variation in cortical excitability, not seen in controls. Paired pulse paradigms, which probe intracortical inhibitory and excitatory circuits, gave results similar to controls. Conclusions We report symptomatic and asymptomatic fluctuations in motor cortex excitability in people with alternating hemiplegia of childhood, not seen in controls. We propose that such fluctuations underlie hemiplegic attacks, and speculate that the asymptomatic fluctuation we detected may be useful as a biomarker for disease activity.

Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT) will develop the post-thrombotic syndrome (PTS). Improving the long-term outcome of DVT patients at risk for PTS will therefore require new approaches. Here we investigate the effects of statins--lipid-lowering agents with anti-thrombotic and anti-inflammatory properties--in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice). Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi) compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1), tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs), and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy.

Background TNFAIP2 is a crucial gene involved in apoptosis. Single nucleotide polymorphisms (SNPs) in its miRNA binding sites could modulate functions of the miRNA-target genes and thus risk of cancers. In this study, we investigated associations between potentially functional SNPs in the miRNA binding sites of the 3′UTR of TNFAIP2 and gastric cancer risk in a US population. Methods We conducted a case-control study of 301 gastric cancer patients and 313 cancer-free controls frequency-matched by age, sex and ethnicity. We genotyped four selected TNFAIP2 SNPs (rs8126 T>C, rs710100 G>A, rs1052912 G>A and rs1052823 G>T) and used the logistic regression analysis to assess associations of these SNPs with cancer risk. Results The rs8126 CC genotype was associated with a significantly elevated risk of gastric cancer (adjusted OR = 2.00, 95% CI = 1.09–3.64 and P = 0.024), compared with the combined rs8126 TT+TC genotypes, particularly in current drinkers. However, none of other TNFAIP2 SNPs was associated with risk of gastric cancer. Conclusions Our data suggested that the TNFAIP2 miRNA binding site rs8126 T>C SNP may be a marker for susceptibility to gastric cancer, and this finding requires further validation by larger studies.

Background Despite many attempts to establish pre-treatment prognostic markers to understand the clinical biology of esophageal adenocarcinoma (EAC), validated clinical biomarkers or parameters remain elusive. We generated and analyzed tumor transcriptome to develop a practical biomarker prognostic signature in EAC. Methodology/Principal Findings Untreated esophageal endoscopic biopsy specimens were obtained from 64 patients undergoing surgery and chemoradiation. Using DNA microarray technology, genome-wide gene expression profiling was performed on 75 untreated cancer specimens from 64 EAC patients. By applying various statistical and informatical methods to gene expression data, we discovered distinct subgroups of EAC with differences in overall gene expression patterns and identified potential biomarkers significantly associated with prognosis. The candidate marker genes were further explored in formalin-fixed, paraffin-embedded tissues from an independent cohort (52 patients) using quantitative RT-PCR to measure gene expression. We identified two genes whose expression was associated with overall survival in 52 EAC patients and the combined 2-gene expression signature was independently associated with poor outcome (P

Background: Perceived stigma and lack of awareness could contribute to the late presentation and low detection rate of tuberculosis (TB). We conducted a study in rural southwest Ethiopia among TB suspects to assess knowledge about and stigma towards TB and their health seeking behavior. Methods: A community based cross sectional survey was conducted from February to March 2009 in the Gilgel Gibe field research area. Any person 15 years and above with cough for at least 2 weeks was considered a TB suspect and included in the study. Data were collected by trained personnel using a pretested structured questionnaire. Logistic regression analysis was done using SPSS 15.0 statistical software. Results: Of the 476 pulmonary TB suspects, 395 (83.0%) had ever heard of TB; "evil eye'' (50.4%) was the commonly mentioned cause of TB. Individuals who could read and write were more likely to be aware about TB [(crude OR = 2.98, (95% CI: 1.25, 7.08)] and more likely to know that TB is caused by a microorganism [(adjusted OR = 3.16, (95% CI: 1.77, 5.65)] than non-educated individuals. Males were more likely to know the cause of TB [(adjusted OR = 1.92, (95% CI: 1.22, 3.03)] than females. 51.3% of TB suspects perceived that other people would consider them inferior if they had TB. High stigma towards TB was reported by 199(51.2%). 220 (46.2%) did not seek help for their illness. Individuals who had previous anti-TB treatment were more likely to have appropriate health seeking behavior [(adjusted OR = 3.65, (95% CI: 1.89, 7.06)] than those who had not. Conclusion: There was little knowledge about TB in the Gilgel Gibe field research area. We observed inappropriate health seeking behavior and stigma towards TB. TB control programs in Ethiopia should educate rural communities, particularly females and non-educated individuals, about the cause and the importance of early diagnosis and treatment of TB.

Blast-associated shock wave-induced traumatic brain injury (bTBI) remains a persistent risk for armed forces worldwide, yet its detailed pathophysiology remains to be fully investigated. In this study, we have designed and characterized a laboratory-scale shock tube to develop a rodent model of bTBI. Our blast tube, driven by a mixture of oxygen and acetylene, effectively generates blast overpressures of 20-130 psi, with pressure-time profiles similar to those of free-field blast waves. We tested our shock tube for brain injury response to various blast wave conditions in rats. The results show that blast waves cause diffuse vascular brain damage, as determined using a sensitive optical imaging method based on the fluorescence signal of Evans Blue dye extravasation developed in our laboratory. Vascular leakage increased with increasing blast overpressures and mapping of the brain slices for optical signal intensity indicated nonhomogeneous damage to the cerebral vasculature. We confirmed vascular leakage due to disruption in the blood-brain barrier (BBB) integrity following blast exposure. Reactive oxygen species (ROS) levels in the brain also increased with increasing blast pressures and with time post-blast wave exposure. Immunohistochemical analysis of the brain sections analyzed at different time points post blast exposure demonstrated astrocytosis and cell apoptosis, confirming sustained neuronal injury response. The main advantages of our shock-tube design are minimal jet effect and no requirement for specialized equipment or facilities, and effectively generate blast-associated shock waves that are relevant to battle-field conditions. Overall data suggest that increased oxidative stress and BBB disruption could be the crucial factors in the propagation and spread of neuronal degeneration following blast injury. Further studies are required to determine the interplay between increased ROS activity and BBB disruption to develop effective therapeutic strategies that can prevent the resulting cascade of neurodegeneration.